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Biomedical subjects

N Panza

Publications and source records attributed to N Panza.

At least 55 records · Page 3Linked to original sources

Effects of lithium treatment on hypothalamic-pituitary-thyroid axis: a longitudinal study.

Lithium carbonate, widely used in the treatment of bipolar patients, is well known to induce thyroid alterations. In this longitudinal study the thyroid function was investigated during lithium treatment over a period of 12 months in 12 euthymic bipolar patients with a normal thyroid function and absence of thyroid antibodies. Nine of the 12 patients were further studied on the 15th month, 5 of these 9 on the 18th month and 4 of the last-mentioned 5 on the 24th month. The mean basal and TRH-stimulated TSH values during lithium therapy were significantly higher as compared to those at the beginning of the treatment. More particularly, during lithium therapy, a significant increase of basal TSH over the normal range was found in 10 out of the 12 patients. A rise of TRH-stimulated TSH was found in 11 out of the 12 patients. The impairment of the hypothalamic-pituitary-thyroid (HPT) axis was transitory in the majority of cases. Two patients developed a nodular goiter during the treatment. Plasma T3, T4, FT3 and FT4 levels did not change during the treatment. Thyroid antibodies remained undetectable. The conclusions of the study are twofold: 1) Subclinical hypothyroidism during lithium therapy is much more frequent than previous cross-sectional studies suggest; 2) Thyroxine replacement in lithium-treated patients is advisable in order to prevent subclinical hypothyroidism and the risk of a subsequent goiter.

Adult↗

Intermediate and high grade malignant non-Hodgkin's lymphomas: preliminary results using a new combination regimen (EVE-COPEM).

Between 1988 and 1992, 60 patients with intermediate and high-grade non-Hodgkin's lymphomas (NHL) were treated with a new multidrug combination chemotherapy including 4'epidoxorubicin (25 mg/m2), etoposide (60 mg/m2), cyclophosphamide (400 mg/m2), administered intravenously (i.v.) on the 1st, 2nd and 3rd day every 4 weeks, prednisone (40 mg/m2) orally for 6 days every 4 weeks, vincristine (1 mg/m2) i.v. and methotrexate (400 mg/m2) i.v. on the 8th day every 4 weeks, vindesine (2.5 mg/m2) and cytarabine (200 mg/m2) on the 15th day every 4 weeks. Patients achieving apparent complete remission (CR) or good partial response (PR) after the 1st cycle of therapy were submitted to three other cycles of the same therapy. Patients failing to respond to the 1st cycle or whose disease progressed despite therapy, were treated with an alternative 2nd line therapy. Seventeen patients (28%) had stage II-II E, 15 (25%) stage III and 28 (47%) stage IV disease. Tumoral mass > 10 cm was found in 28 cases, the presence of extranodal sites (ES) in 32 cases, serum lactate dehydrogenase (LDH) > 240 IU/l in 34 cases, performance status (PS) > or = 2 in 12 cases. CR was obtained in 46 (76.4%) out of the 60 patients. Relapse-free survival (RFS) was 82, 64 and 61% with a median follow-up of 12, 24 and 36 months respectively. No relapse occurred later than 26 months after achievement with CR thus far. Overall survival (OS) was 77% at 12 months and calculated to be 62% and 59% at 24 and 36 months, respectively. Two patients died as a result of the treatment. Reversible myelosuppression was the main toxic effect. One hundred and ten out of the 221 cycles of chemotherapy were delayed because of therapy toxicity. Negative prognostic factors on the RFS and OS were the presence of an advanced stage of disease, a mass larger than 10 cm, the presence of ES, the elevated LDH, the PS > or = 2, the delay of therapy. In conclusion, results obtained using our protocol overlap those from other third generation regimens. Toxicity was also similar. The influence of clinical conditions such as stage of disease, the presence of ES, high LDH level and tumoral mass > 10 cm on the RFS and OS were significant. Principal variables influencing prognosis must be unified to compare results of similar treatments from different institutions.

Adult↗

Clinical management of prolactinomas: a ten-year experience.

A ten-year experience on 36 patients bearing macroprolactinomas (MP) and 86 others bearing microprolactinomas (mP) is reported in this study. Different therapeutical approaches were used: 1) trans-sphenoidal surgery in 24 patients with MP and in 25 with mP; 2) medical therapy with the oral form of bromocriptine (BRC) in all the 24 patients with MP previously subjected to surgery, in 48 patients with mP ab initio, and in 16 out of 25 patients with mP previously subjected to surgery; 3) medical therapy with the long-acting injectable forms of BRC in 12 MP- and 13 mP-bearing patients, and 4) conventional radiotherapy in 12 of the 24 patients with MP previously subjected to surgery. The follow-up, performed five years after surgery, showed that: a) all the 24 patients with MP but one had normal PRL levels during BRC administration, with a rebound of hyperprolactinemia in all cases after withdrawal; b) during the treatment BRC caused normalization of PRL in 15 of the 16 mP-bearing patients surgically treated and in all the 48 mP-bearing patients only treated with BRC; c) in 20 of the 25 patients the treatment with injectable retard BRC caused the normalization of plasma PRL and the shrinkage of the tumor mass in all the patients with MP but one, as revealed by seriate CT scans. In conclusion, the surgical treatment of prolactinomas was ineffective to normalize plasma PRL levels in most patients whereas BRC, in standard or in retard forms, was able to normalize plasma PRL levels, reduce the tumoral mass and preserve the pituitary residual tissue. BRC should be, therefore, used as first choice therapy both for MP and mP.

Adolescent↗

Hormonal and immunological pattern in a patient with acquired immunodeficiency syndrome related complex and Cushing's syndrome.

A case of Cushing's syndrome in a 24-yr-old homosexual with an AIDS-related complex is reported. In this patient certain symptoms common to both diseases, i.e. weakness, myalgia and muscle atrophy were accentuated, whereas other symptoms pathognomic of the human immunodeficiency virus (HIV) infection, i.e. lymphoadenopathies and weight loss, were less pronounced by the high levels of circulating adrenal steroids. Ketoconazole was administered po in order to block adrenal steroidogenesis, the drug caused a remarkable fall of cortisol serum concentrations, but was unable to modify significantly the immunological pattern of the patient. Our data suggest that changes of serum adrenal steroid levels have little effect on the immune network of patients with AIDS.

AIDS-Related Complex↗

Management of patients with ovarian cancer using monoclonal antibodies.

We describe in detail the current trend using monoclonal antibodies to diagnose ovarian cancer either in vitro or in vivo. The approach with such powerful reagents allows to differentiate in vitro tumor histotypes and to detect in peritoneal washings the presence of a few neoplastic cells which characterize the minimal disease. The detection of elevated sera levels of ovarian cancer-associated antigens, such as CA-125 and TAG-72, allows the monitoring, follow-up of these patients and the response to therapy with great accuracy. We focused our attention on the role in vivo of labelled monoclonal antibodies, mainly for diagnostic purposes. Radioimmunoscintigraphy has been found to be more reliable than CT and US to detect foci of disease mainly in patients already treated by surgery, overcoming all the problems usually encountered with these two procedures.

Antibodies, Monoclonal↗

(131I)meta-iodobenzylguanidine scintigraphy and selective venous catheterization after thyroidectomy for medullary thyroid carcinoma.

Fifteen patients with medullary carcinoma of the thyroid (MCT), who had persistently elevated levels of serum calcitonin (CT) and carcinoembryonic antigen (CEA) after total thyroidectomy, were studied in order to localize the sites of the recurrent disease. Routine diagnostic examinations, including ultrasonography (US) and computed axial tomography (CAT), were carried out in all the cases. Scintigraphy with radio-iodinated metaiodobenzylguanidine ((131I)-MIBG) was performed in 13 cases; selective venous catheterization (SVC) to reveal a gradient of CT levels was performed in 12 cases. Ten patients underwent both (131I)-MIBG scintigraphy and SVC. US and CAT revealed the sites of recurrent tumor in only 4 out of the total 15 patients. SVC in basal conditions showed the presence of small metastases in 2 cases, and after intravenous stimulus with pentagastrin in 4 others. The MIBG scan showed metastatic foci of sporadic MCT in 2 patients, residual medullary thyroid tissue in 4 others, and a pheochromocytoma in a previously undiagnosed patient with Sipple's syndrome. More particularly, MIBG scan and SVC showed the localization of residual or metastatic tumor in 10 cases. In all 10 cases, results of the MIBG scan and SVC were confirmed as true positive by subsequent surgery and histopathologic examination.(ABSTRACT TRUNCATED AT 250 WORDS)

3-Iodobenzylguanidine↗

The biological approach to radioimmunoscintigraphy.

The authors have analysed the theoretical and clinical implications of a biological approach to radioimmunoscintigraphy (RIS), a new diagnostic technique based on the in vivo reaction between radiolabelled monoclonal antibodies and tumor-associated antigens expressed by the neoplastic cells. The assumption is that, as in all radioisotopic procedures, the radioimmunoscintigraphic image is the expression of differences in concentration (and not in density) between adjacent tissues. This "biological premise" is analysed to demonstrate a possible role of RIS not only in diagnosis but also in prognosis and therapy. A comparison with other imaging procedures and with histopathology, considered as the "gold standard" of the present-day morphological approach to diagnosis, is also discussed. Finally, biological premises, as well as the initial results and prospects regarding the use of high doses of radiolabelled monoclonal antibodies for therapeutic purposes are presented.

Antibodies, Monoclonal↗

Diagnosis of ovarian cancer with radiolabelled monoclonal antibodies: our experience using 131I-B72.3.

Radioimmunoscintigraphy (RIS) using 131I-labelled B72.3, a monoclonal antibody (MoAb) reacting against a tumor associated antigen (TAA) called TAG-72, has been performed in 36 patients with epithelial ovarian cancer. The patients were divided in three groups as follows: 17 patients with primary cancer before any therapy (Group 1); 10 patients studied after a partial therapeutic approach, having either bulky or minimal disease (Group 2); 9 patients with microscopic disease or in clinical remission at the moment of the study (Group 3). All the most important epithelial histotypes, including mucinous, were present. Results were confirmed at surgery and/or by other diagnostic procedures. Immunocytochemical (ICC) and immunocytofluorimetric (ICF) studies on ascitic collections were performed in order to demonstrate specificity of B72.3 and TAG-72 distribution on neoplastic cells. Immunohistochemistry (IHC) on tissue sections was also obtained. No cross reactions between B72.3 and mesothelial cells in the presence of specific uptake by neoplastic cells was found. Moreover, a non-homogeneous distribution of TAG-72 in the neoplastic population was demonstrated by ICF. RIS proved the intraperitoneal presence of disease in 15 out of 17 and in 5 out of 10 patients in Groups 1 and 2, respectively. One out of four (Group 1) and two out of four (Group 2) extraperitoneal metastases were also seen. False negative results were explained by lack of expression of the antigen, size and location of the lesion, and patho-physiological conditions. One false positive due to an aspecific uptake by a post-surgical active scar was also observed in a disease-free patient.

Antibodies, Monoclonal↗

Cancer antigen 125, tissue polypeptide antigen, carcinoembryonic antigen, and beta-chain human chorionic gonadotropin as serum markers of epithelial ovarian carcinoma.

Cancer antigen 125 (CA 125) is common to most epithelial ovarian tumors. Therefore, it is potentially a good marker of this disease. This hypothesis was evaluated by measuring the serum levels of CA 125 in 81 patients with ovarian cancer (25 with nonactive and 56 with active disease), in 105 patients of both sexes with nonovarian tumors, and in 171 healthy controls of both sexes. The serum levels of three other markers, tissue polypeptide antigen (TPA), carcinoembryonic antigen (CEA), and human chorionic gonadotropin, beta subunit (beta-hCG), were also measured in the same 357 subjects. The results of this study clearly indicate the clinical irrelevance of both CEA and beta-hCG as tumor markers in ovarian carcinomas. Conversely, the clinical usefulness of CA 125 and TPA was confirmed. In particular, CA 125 and TPA showed comparable sensitivity, while CA 125 showed a higher specificity for ovarian cancer than TPA. The association of CA 125 with TPA was very useful in continuous observation of patients with active disease in order to evaluate the clinical effectiveness of the therapy. Moreover, for patients in clinical remission, the markers allowed early detection of a recurrence of the disease.

Adult↗

Transglutaminase in cell proliferation and transformation.

Transglutaminase (TGase) activity was reduced in intact mitogen-stimulated human peripheral blood lymphocytes (PBL) when compared to intact resting PBL. Moreover, a treatment of the same quiescent immunocompetent cells with purified liver TGase and Ca2+ completely suppressed the mitogen-induced blast transformation. A decrease in TGase activity in neoplastically transformed seminal vesicle epithelial cells with respect to their normal parent counterpart was also observed. Our data support the notion of a possible implication of TGase in cell proliferation and transformation.

Animals↗

A prospective imaging study of 131I-B72.3 monoclonal antibody in patients with epithelial ovarian cancer: preliminary report.

Twenty patients with known ovarian cancer have been investigated in this pilot study to verify the clinical usefulness of radioimaging using the B72.3 monoclonal antibody labelled with iodine-131. No adverse reactions occurred after intravenous injection of B72.3 MoAb. The radioimaging results were compared with those obtained with other diagnostic methods, including computed X-ray tomography and ultrasound. A sensitivity of 85% in the detection of primary ovarian cancers and collections of ascites, and of 84% in the detection of abdominal and extraperitoneal metastases has been demonstrated using this radioiodinated antibody in vivo. No false localization occurred. Immunohistochemical studies showed no cross-reactions between B72.3 MoAb and mesothelial cells, confirming the high specificity of binding between B72.3 MoAb and neoplastic cells in ascites. Negligible uptake of radiolabelled B72.3 MoAb has been demonstrated in the unaffected ovary. The major advantage of using this monoclonal antibody is related to the expression of a recognized antigen (called TAG 72) in mucinous, serous and in differentiated adenocarcinomas of the ovary.

Abdominal Neoplasms↗

High serum thyroglobulin levels. Diagnostic indicators in patients with metastases from unknown primary sites.

Patients with metastases from differentiated thyroid carcinoma have a good chance of long-term survival when the diagnosis is prompt and appropriate therapy is applied early. This is also true for patients with metastases in the bone, taking into account that an appropriate therapy, usually 131-I, may be palliative in some cases. This study investigates whether serum thyroglobulin (Tg) measurement in patients with cold thyroid nodule and metastases from an unknown primary site could help identify a differentiated thyroid carcinoma. The results obtained show that Tg measurements is a useful adjunctive test when used with fine-needle aspiration biopsy. In particular, very high Tg levels point to metastatic thyroid cancer, whereas lower levels do not help determining whether metastatic cancer is of thyroid origin or not.

Biomarkers, Tumor↗

Prolactin and TSH response to TRH and metoclopramide before and after l-thyroxine therapy in subclinical hypothyroidism.

The effects of the dopamine (DA) receptor antagonist metoclopramide on the plasma thyroid stimulating hormone (TSH) and prolactin (PRL) levels were studied in 8 patients with subclinical hypothyroidism (defined as absence of clinical signs of hypothyroidism with normal thyroid hormone levels, normal or slightly increased basal plasma TSH levels and increased and long-lasting TSH response to TRH) before and after l-thyroxine replacement therapy. Metoclopramide induced a significant (p less than 0.01) TSH release in the subclinical hypothyroid patients. Two weeks after l-thyroxine replacement therapy (50 micrograms/day), the TSH response to metoclopramide was completely blunted in subclinical hypothyroidism. In these patients a significant (p less than 0.01) inhibition of TSH response to intravenous thyrotropin-releasing hormone (TRH) was also observed after treatment with thyroid hormone. In analogy to the TSH behavior, plasma PRL secretion in response to metoclopramide and TRH administration was significantly (p less than 0.05) inhibited in the subclinical hypothyroid patients after l-thyroxine replacement therapy.

Adult↗

Pseudotumor cerebri and thyroid-replacement therapy in patients affected by differentiated thyroid carcinoma.

The pseudotumor cerebri, a neurological syndrome clinically characterized by headaches, vomiting and bilateral papilledema, occurred in two patients, previously subjected to total thyroidectomy for differentiated thyroid carcinoma, after initiation of levothyroxine replacement therapy. In patients with thyroid cancer, subjected to thyroidectomy and then thyroid hormone replacement therapy, the possible development of pseudotumor cerebri syndrome should be considered and differentiated from CNS symptoms due to brain metastases.

Adenocarcinoma↗

Inhibition of cyclophosphamide mutagenicity by beta-carotene.

Cyclophosphamide (CP) metabolites, rather than the parent compound, show mutagenic activity towards Salmonella typhimurium TA 1535 tester strain when S9 fraction from phenobarbital (PB)-induced rat liver is used as in vitro metabolizing system. On the other hand, inhibition of CP in vitro mutagenicity was observed by adding increasing amounts of beta-carotene (beta-C) to the system. A typical dose-dependent mutagenic response was observed by assaying 24 h urine samples of PB-induced rats injected i.p. with different amounts of CP. Addition of beta-C to urines of CP-treated rats failed to inhibit their mutagenicity. Conversely, a marked decrease in urine mutagenicity was observed when rats were simultaneously treated with the two drugs. These data show that beta-carotene partially inhibits, in vitro and in vivo, CP metabolism via hepatic mixed-function oxidase enzymes to mutagenic species.

Animals↗

Effect of beta-carotene on mutagenic activity of some antineoplastics.

Mutagenic activity on Salmonella typhimurium strains of some cytostatic drugs in the absence and in the presence of beta-carotene was evaluated. Cyclophosphamide mutagenicity was reduced by the retinoid both in vitro and in vivo. Conversely, its metabolite 4'-hydroxy-cyclophosphamide, which does not require enzymatic transformation to exert genotoxic activity against bacteria, was not affected by the presence of beta-carotene. Moreover, the mutagenic activity of cis-Platinum, Adriamycin and 4'Epiadriamycin, which are typical direct-acting mutagens, was not affected by beta-carotene. Data obtained confirm that beta-carotene is able to prevent mutagenic activity of cyclophosphamide by interfering with its metabolic activation but failed to inhibit the interaction of genotoxic compounds with bacterial DNA.

Animals↗